Objective: To study the role of cyclic nucleotides in the control mechanisms of neuroblastoma cells in culture. Approach: We have some data to indicate cyclic AMP may be involved in the "differentiation" of mouse neuroblastoma cells in culture. Analogous experiments will be performed on human neuroblastoma cells in order to evaluate the role of cyclic AMP. The following studies will be completed: (a) Correlation between morphological differentiation and cyclic AMP level. (b) Relationship between the cyclic AMP level and the levels of adenylate cyclase (AC) and cyclic AMP phosphodiesterase (PDE). (c) Changes in the levels of cyclic AMP, AC and PDE as a function of cell cycle. (d) Levels of cyclic AMP, AC and PDE in morphologically "differentiated" cells induced by non-cyclic AMP agents (x-ray, 5-bromodeoxyuridine, 6-thioguanine, serum-free medium and nerve growth factor). We will investigate the relative sensitivity of adenylate cyclase of various clones to catecholamines and acetylcholine.